Serious body trauma caused by extensive battlefield injuries, such as that arising from high-velocity gunshot wounds, can lead to the loss of bone. In particular, battlefield activities can leave participants in need of having bones repaired by grafting. Autologous and cadaveric bone are considered the gold-standard bone graft materials. Their advantage is that they retain osteogenetic, osteoinductive, and osteoconductive properties that are required for bone regeneration. However, due to the nature of their harvesting, only a limited amount of bone tissue can be extracted. For autologous bone, detrimental side effects such as discomfort, donor site morbidity, secondary surgical procedures and risk of patient mortality or weakness resulting in fracture can occur. Allograft bone risks the transfer of antigens/disease, improper bone bonding, uncontrolled resorption and subsequent graft failure.
One specific area of interest is spinal fusion surgery, where it is estimated that more than 200,000 of these surgeries are performed each year in the United States alone, and this number continues to rise. Spinal fusion surgeries consist of removing an intervertebral disc and fusing the adjoining vertebrae. Current surgery implants include autografts and allografts. An additional surgery to remove bone from the iliac crest of the pelvic girdle is required for autografts. Its use has the significant advantage of reduced rejection by the patient. But many patients experience discomfort or donor site morbidity as a result of the extra procedure, while others may not have enough bone available for removal. Risks associated with allografts include disease transmission, supply limitations, and poor natural bone growth, or uncontrolled re-sorption after fusion surgery. At its optimum, a graft should be resorbed in such a manner that it allows sufficient time and structure for vascularization of the porosities and subsequent bone ingrowth.
There is significant demand for large scale, bioresorbable, biocompatible, and bioactive bone graft substitute materials (BGSM). Synthetic calcium phosphates represent an option for BGSM. Currently available synthetic calcium phosphate bone graft materials are limited to specific chemistries of calcium and phosphate due to the nature of their manufacturing processes (wet chemistry precipitation, sol-gel, sintering, ashing of bovine or human bone). In reality, the mineral phase of bone has a complex chemistry, in addition to significant mechanical, biological and material properties.
Currently available synthetic calcium phosphate bone graft materials are limited to specific chemistries of calcium and phosphate due to the nature of their manufacturing processes. Two main methods are currently used to produce synthetic calcium phosphate bone graft materials. Some methods are wet methods, such as aqueous precipitation, gel casting, slurry dipping, spraying, sol-gel processes, or hydrolysis of calcium phosphates. A disadvantage of wet methods is that it can take weeks to produce small quantities of product. The second method utilizes solid-state reactions, which include uniaxial or isostatic compaction of loose powders, followed by a heat treatment. Other solid-state reactions include hot pressing, 3-dimensional laser printing and selective laser sintering. Solid-state reactions require high production time, cost and labor for bulk production and require multiple heat treatments to produce.
In addition to the need for bone graft materials, there is also a need for those BGSM to be resistant to microbial growth. Postoperative infections caused by gram positive bacteria (e.g. S. aureus, S. epidermidis, Streptococcus spp.) are one of the biggest challenges in battlefield orthopedic surgery. Incorporation of a localized antibiotic component, such as ionic sliver, within the implant could reduce the incidence of infection. Ionic silver is considered to have a broad spectrum of antimicrobial properties at concentrations as low as about 35 ppb without toxic effects to mammalian cells. It has been shown that silver (Ag) ions and Ag-based composites are highly toxic to microorganisms and incorporation of an antimicrobial component, for example silver based antimicrobial components, in the BGSM could create a localized antibiotic effect.
What is needed is a self-propagating reaction process that would provide the ability to synthesize calcium phosphate materials that could be incorporated into bone, bone grafts, or used as a filter. Ideally, the chemistry of the calcium phosphates could be tailored to suit the type of bone that is being grafted. Furthermore, it would be ideal if dopants, such as antimicrobial agents or materials that alter the BGSM properties, could be combined in the synthesis process and incorporated into the final product. Finally, it would be desirable to develop a process that would produce materials to deliver a controlled dose of an antimicrobial agent over time.